The regulation of DOCK family proteins on T and B cells.

The dedicator of cytokinesis (DOCK) family proteins consist of 11 members, each of which contains 2 domains, DOCK homology region (DHR)-1 and DHR-2, and as guanine nucleotide exchange factors, they mediate activation of small GTPases. Both DOCK2 and DOCK8 deficiencies in humans can cause severe combined immunodeficiency, but they have different characteristics. DOCK8 defect mainly causes high IgE, allergic disease, refractory skin virus infection, and increased incidence of malignant tumor, whereas DOCK2 defect mainly causes early-onset, invasive infection with less atopy and increased IgE. However, the underlying molecular mechanisms causing the disease remain unclear. This paper discusses the role of DOCK family proteins in regulating B and T cells, including development, survival, migration, activation, immune tolerance, and immune functions. Moreover, related signal pathways or molecule mechanisms are also described in this review. A greater understanding of DOCK family proteins and their regulation of lymphocyte functions may facilitate the development of new therapeutics for immunodeficient patients and improve their prognosis. ©2020 Society for Leukocyte Biology.